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Inhibition of HERG Potassium Channels by Domiphen Bromide and Didecyl Dimethylammonium Bromide

Inhibition of HERG Potassium Channels by Domiphen Bromide and Didecyl Dimethylammonium Bromide

Yan Long, Wanjuan Chen, Zuoxian Lin, Hongmao Sun, Menghang Xia, Wei Zheng, Zhiyuan Li

Eur J Pharmacol. 2014 Aug 15;737:202-9.

PMID: 24846011

Abstract:

Domiphen bromide and didecyl dimethylammonium bromide were widely used environmental chemicals with potent activity on blockade of human ether-a-go-go related gene (HERG) channels. But the mechanism of their action is not clear. The kinetics of block of HERG channels by domiphen bromide and didecyl dimethylammonium bromide was studied in order to characterize the inhibition of HERG currents by these quaternary ammonium compounds (QACs). Domiphen bromide and didecyl dimethylammonium bromide inhibited HERG channel currents in a dose-dependent manner with IC50 values of 9nM and 5nM, respectively. Block of HERG channel by domiphen bromide and didecyl dimethylammonium bromide was voltage-dependent and use-dependent. Domiphen bromide and didecyl dimethylammonium bromide caused substantial negative shift of the activation curves, accelerated activated process, but had no effects on the deactivation and reactivation processes. The docking models implied that these two compounds bound to PAS domain of HERG channels and inhibited its function. Our data demonstrated that domiphen bromide and didecyl dimethylammonium bromide blocked the HERG channel with a preference for the activated channel state.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP6912125	Dimethylammonium bromide		6912-12-5	Price

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